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ToxSci Advance Access originally published online on February 16, 2008
Toxicological Sciences 2008 103(2):228-240; doi:10.1093/toxsci/kfn033
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

miRNAs: Effectors of Environmental Influences on Gene Expression and Disease

Alice Hudder and Raymond F. Novak1

Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan 48201-2654

1 To whom correspondence should be addressed at Institute of Environmental Health Sciences, Director, EHS Center for Molecular and Cellular Toxicology with Human Applications, 2727 Second Avenue, Room 4000, Detroit, MI 48201-2654. Fax: (313) 577-0082. Email: r.novak{at}wayne.edu.

Received January 16, 2008; accepted February 10, 2008


  Abstract

Discovered less than a decade ago, micro-RNAs (miRNAs) have emerged as important regulators of gene expression in mammals. They consist of short nucleic acids, on average ~22 nucleotides in length. The miRNAs exert their effect by binding directly to target messenger RNAs (mRNAs) and inhibiting mRNA stability and translation. Each miRNA can bind to multiple targets and many miRNAs can bind to the same target mRNA, allowing for a complex pattern of regulation of gene expression. Once bound to their targets, miRNAs can suppress translation of the mRNA by either sequestration or degradation of the message. Thus, miRNAs function as powerful and sensitive posttranscriptional regulators of gene expression. This review will summarize what is known about miRNA biogenesis, expression, regulation, function, mode of action, and role in disease processes with an emphasis on miRNAs in mammals. We discuss some of the methodology employed in miRNA research and the potential of miRNAs as therapeutic targets. The role of miRNAs in signal transduction and cellular stress is reviewed. Lastly, we identify new exciting avenues of research on the role of miRNAs in toxicogenomics and the possibility of epigenetic effects on gene expression.

Key Words: micro-RNAs; translational control; signaling; polysomes; cytochrome P450; toxicants.


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